Prevention of ischemia-reperfusion injury in a rat skill flap model: The role of mast cells, cromolyn sodium, and histamine receptor blockade

The objective of this study was to examine the role of mast cells and their principal product, histamine, in ischemia/reperfusion injury. Cromolyn sod ium, diphenhydramine, and cimetidine were administered to ischemic flaps ju st before repel-fusion and evaluated for flap survival, mast cell count, ne utrophil count, and myeloperoxidase levels. Epigastric island skin flaps we re elevated in 49 rats; they were rendered ischemic by clamping the artery for 10 hours. Thirty minutes before reperfusion, the rats were treated with intraperitoneal saline (n = 11), cimetidine (n = 11), diphenhydramine (n = 11), or cromolyn sodium (n = 10). Flap survival was evaluated at 7 days. N eutrophil counts, mast cell counts, and myeloper-oxidase levels were evalua ted 12 hours after reperfusion. Flap necrosis in the sham group of animals (n = 6) was 0.0 percent, as expected, whereas the control group (saline-tre ated animals) had 47.3 +/- 33.4 percent necrosis. Animals treated with diph enhydramine and cimetidine demonstrated a significant decrease in flap necr osis to 17.7 +/- 8.8 percent and 19.4 +/- 14.7 percent, respectively. This protective effect was not seen with cromolyn sodium (44.3 +/- 35.6 percent) . Both neutrophil and mast cell counts were significantly decreased in flap s from antihistamine-treated and sham animals versus both saline- and cromo lyn sodium-treated groups. The administration of diphenhydramine and cimetidine before reperfusion can significantly reduce the extent of flap necrosis and the neutrophil and ma st cell counts caused by ischemia/reperfusion. This protective effect is no t seen with cromolyn sodium. The protective effect of antihistamines on fla p necrosis might be related to the decrease in neutrophils and, possibly, m ast cells within the flap.